Fat has been villainized; but all fat was not created equal. Our two main types of fat—brown and white—play different roles. Now, two teams of NIH-funded researchers have enriched our understanding of adipose tissue. The first team discovered the genetic switch that triggers the development of brown fat [1], and the second figured out how the body can recruit white fat and transform it into brown [2].

Why would we want to change white fat into brown? White fat stores energy as large fat droplets, while brown fat has much smaller droplets and is specialized to burn them, yielding heat. Brown fat cells are packed with energy generating powerhouses called mitochondria that contain iron—which gives them their brown color. Infants are born with rich stores of brown fat (about 5% of total body mass) on the upper spine and shoulders to keep them warm. It used to be thought that brown fat disappeared by adulthood—but it turns out we harbor small reserves in our shoulders and neck.

In mice, brown fat does something remarkable: it burns more calories when mice are overfed, protecting them from obesity. (Don’t you wish eating a plate of fries did that for you?) Furthermore, mice genetically predisposed to have with extra brown fat are actually leaner and healthier. In humans, there is evidence that more brown fat is associated with a lower body weight. So, how might we increase our brown fat production?

The team led by the University of Pennsylvania figured out the switch for creating a brown fat cell—a protein called early B cell factor-2 (Ebf2). Comparing the active genes in brown and white fat cells, they discovered Ebf2 is present in larger quantities in brown fat. This protein seems to mark which genes will later be turned on to transform certain types of precursor cells into brown fat. When the team engineered mice lacking this protein, the animals had white fat cells on their upper back and spine rather than the typical brown. When the team expressed high levels of Ebf2 in white fat, these cells turned brown and consumed more oxygen—a sign they were producing more heat.

The second team, led by Harvard’s Joslin Diabetes Center, noted that mice have two types of brown fat: constitutive brown fat, which they have from birth, and “recruitable” brown fat, scattered throughout the muscles and white fat. When researchers engineered mice lacking a protein called Type 1A BMP-receptor (BMPR1A)—which is needed for the correct development of brown fat—the mice were born with just a tiny bit of constitutive brown fat on their back.

You would think that these mice would be terribly cold. Surprisingly, they kept a normal body temperature. How did they manage this feat?

The lack of brown fat apparently sends a signal via the brain to the recruitable fat cells, telling them to make the switch and transform into brown fat. The mice stayed warm, and the recruited brown fat even protected them from obesity.

In humans, too much abdominal white fat promotes heart disease, diabetes, and many other metabolic diseases. It would be potentially therapeutic if we could transform some of our white fat into brown. Determining which genes control the development of white and brown fat may be the first step toward developing game changing treatments for diabetes and obesity.

23 Comments

Extremely interesting article given the increase prevalence of obesity. It would also be interesting to see whether lifestyle can have any influence on the expression of these genes once when they are being identified.
Will definitely stay tuned.

Thanks for your question, Jorge Luis. The work highlighted by Dr. Collins involved genetically engineered mice. So, more research needs to be done before we can consider transforming white fat into brown fat in humans.

Good question, James! Because the studies mentioned in this blog post were done in genetically engineered mice, they tell us very little, if anything, about the health effects, good or bad, of liposuction in humans.

Looking for a ‘game changing’ treatment for diabetes and obesity? You don’t have to wait for any pie-in-the-sky gene therapies, either. Rather, you can read right now the study that was published May 2009 in The American Journal of Clinical Nutrition, Dr. Neal Barnard as principal investigator, entitled ‘A low-fat vegan diet and a conventional diabetes diet in the treatment of type-2 diabetes; a randomized, controlled 74-week clinical study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677007/

Thanks for sharing this study, Lawrence. For anyone who might be interested,the study’s conclusions were as follows:

Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.

My brother and sister-in-law have been on the Dr. Atkins Diet for almost two years, now on the maintenance portion. Both have eliminated body fat, high cholesteral levels and abdominal fat! She has reduced her dependence on insulin, now considered non-diabetic. At 67, they are both healthy. How can this be explained?

Wondering if the reduction of brown fat over years or, its reverse, building up brown fat, can help regulate body temperature in the aging population? This would seem useful for older people that struggle to stay warm. Interesting long term applications….

I would be interested in how they are going to go forward with their research. Is the next step human studies or do they go onto other mammals? I guess it will be a long time before we get any firm findings, but I would definitely love to hear more about it. Although I do think that obesity and heart disease can be controlled by healthier eating in general.

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About the NIH Director

Francis S. Collins, M.D., Ph.D.

Appointed the 16th Director of NIH by President Barack Obama and confirmed by the Senate. He was sworn in on August 17, 2009. On June 6, 2017. President Donald Trump announced his selection of Dr. Collins to continue to serve as the NIH Director.